Licit psychostimulant consumption in Australia, : international and jurisdictional comparison

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1 RESEARCH Licit psychostimulant consumption in Australia, : international and jurisdictional comparison Constantine G Berbatis, V Bruce Sunderland and Max Bulsara STANDARDISED DATA have been lacking to reliably test differences in the consumption The Medical of psychostimulants Journal of Australiafor the treatment ISSN: X of attention 18 November deficit 2002 hyperactivity 177 disorder (ADHD). This study is the first The standardised Medical Journal analysis of Australia of drug consumption Research data from statutory international and national sources, and forms a reference for evaluating use of these drugs. The centrally acting psychostimulant drugs methylphenidate and dexamphetamine are the preferred pharmacotherapies for ADHD in children in North America, 1 the United Kingdom 2 and Australia. 3 The safety of these agents used long term, 1 their use in children aged under six years, 4 the variable methodology in clinical trials, 2,5 the sequential or combined use of drug and non-drug approaches, 3,5 and misuse of these drugs 6 are issues of concern. Results of large controlled studies have confirmed that psychostimulants are efficacious treatments in defined patients who are accurately diagnosed and whose treatment has been rigorously assessed. 2,5 Dexamphetamine is the only psychostimulant available through Australia s Pharmaceutical Benefits Scheme (PBS). PBS prescribing of dexamphetamine requires approval in States and Territories of patients and prescribers (usually psychiatrists and paediatricians). ADHD and narcolepsy are the only approved PBS indications, with ADHD the dominant use. Since 1990, increasingly high rates of psychostimulant prescribing to children and of doctors consultations for ADHD have been reported in the United States and Australia. 1,3,7-10 ABSTRACT Curtin University of Technology, Perth, WA. Constantine G Berbatis, BSc, MSc, Lecturer, School of Pharmacy; V Bruce Sunderland, PhD, FPS, Professor and Head, School of Pharmacy. University of Western Australia, Perth, WA. Max Bulsara, BSc(Hons), MSc, Biostatistician, School of Population Health. Reprints will not be available from the authors. Correspondence: Mr C G Berbatis, Curtin University of Technology, GPO Box U1987, Perth, WA berbatis@git.com.au Objectives: To examine trends in the licit consumption of the psychostimulants dexamphetamine and methylphenidate in Australia and nine other countries from 1994 to 2000 and in each State and Territory of Australia from 1984 to Design: Annual rates of consumption of psychostimulants were compared using Poisson regression models. All drug consumption was standardised to defined daily doses per 1000 population per day. Main outcome measures: Rates of consumption of each psychostimulant in each country and in each Australian State and Territory. Results: For the 10 countries from 1994 to 2000, total psychostimulant consumption increased by an average 12% per year, with the highest increase from 1998 to Australia and New Zealand ranked third in total psychostimulant use after the United States and Canada. Australia consumed significantly more than the United Kingdom, Sweden, Spain, the Netherlands, France or Denmark. In Australia, from 1984 to 2000, the rate of consumption of licit psychostimulants increased by 26% per year, with an 8.46-fold increase from 1994 to Western Australia ranked first, with nearly twice the consumption rate of total psychostimulants as New South Wales, which ranked second. Methylphenidate is the main psychostimulant consumed in the US and Canada, and dexamphetamine in Australia. Conclusions: The consumption of psychostimulants in Australia is high internationally and varies significantly between States and Territories. The results imply varied jurisdictional prescribing determinants and supply processes throughout Australia, which may require new national prescribing standards and access to online patient data for prescribers and dispensers. Because of its PBS listing and longer half-life, use of dexamphetamine outgrew the use of methylphenidate. 11 Prescribing of these drugs in Australia is controlled by a few specialists. 12 Studies on the characteristics of ADHD and psychostimulant use are difficult to compare because of the different units, varying age groups studied and differing methods used A lack of standardisation in Australian and international studies underlies the few reported comparisons of regional 8 or international 12 consumption of psychostimulants and hinders the evaluation of prescribing practices and prescription drug misuse. The aims of this study are to compare trends from 1994 to 2000 in the rates of consumption of dexamphetamine and methylphenidate in Australia with nine other developed countries, and to compare the rates of their consumption between Australia s jurisdictions (States and Territories) from 1984 to METHODS MJA Vol November Methods MJA 2002; 177: International data on the consumption of licit drugs of dependence are held by the International Narcotics Control Board (INCB), 15 which publishes yearly reports, with statistics received from about 160 member countries, including the Treaties and Monitoring Unit

2 1: Rate ratios (RR) of total licit psychostimulant consumption in Australia (1.0) compared with nine other countries for Canada (RR, 2.01; 95% CI, ) Denmark (RR, 0.10; 95% CI, ) France (RR, 0.01; 95% CI, ) Netherlands (RR, 0.38; 95% CI, ) New Zealand (RR, 0.78; 95% CI, ) Spain (RR, 0.15; 95% CI, ) 2: Standardised total licit consumption of psychostimulants in Australia, DDDs/1000 per day Sweden (RR, 0.04; 95% CI, ) United Kingdom (RR, 0.59; 95% CI, ) United States (RR, 3.61; 95% CI, ) Source: International Narcotics Control Board, Rate ratio Year Dexamphetamine: Western Australia Dexamphetamine: Australia (except Western Australia) Methylphenidate: Western Australia Methylphenidate: Australia (except Western Australia) DDD = defined daily dose. Source: International Narcotics Control Board, (TMU) in Australia s Commonwealth Department of Health and Ageing. 16 The INCB and TMU are, respectively, the most reliable international and jurisdictional sources of consumption of these agents. 16 Data on total yearly dexamphetamine and methylphenidate consumption for Australia and nine other developed countries from 1994 to 2000 were obtained from the INCB and standardised. Canada, Denmark, France, the Netherlands, New Zealand, Spain, Sweden, the United Kingdom and the US were selected because they are developed countries and their annual data have for many years been audited by the INCB. Annual data from 1984 to 2000 on dexamphetamine sulfate 5 mg tablets and methylphenidate 10 mg tablets were obtained from the TMU and standardised to defined daily doses (DDDs) per 1000 population per day using interpolations of end-year national and Australian jurisdictional populations. The methods have been previously reported. 16 The DDDs for dexamphetamine of 15 mg and for methylphenidate of 30 mg have been set by the World Health Organization Collaborating Centre for Drug Statistics Methodology. 17 Poisson regression models 18 were used for all statistical analyses of DDD rates by country and by Australian jurisdiction. Total populations for each country and jurisdiction in each calendar year were used as the denominator. The natural logarithm of the denominator was used as the offset variable in the Poisson regression analysis. Rate ratios (RRs) and their 95% confidence intervals are reported. Overall consumption rates are based on aggregates over the entire study period. Because of the overdispersion of data, a Pearson s scale factor was used. All the regression analysis was done using SAS (Proc Genmod). 19 The relative risks (RRs) were calculated for each country in the international comparison and for each jurisdiction in Australia. In the international analysis, Australia was attributed a rate ratio of 1.0. In the national analysis, New South Wales was assigned a rate ratio of 1.0. RESULTS 1.Results International analysis From 1994 to 2000, for the 10 countries studied, there was a significantly increased trend in consumption of dexamphetamine and methylphenidate of an average 12% per year (RR, 1.12; 95% CI, ). The US consumed nearly four times the DDD/1000 population per day more than Australia, and Canada consumed twice as much as Australia and New Zealand. All other countries consumed significantly less than Australia. France, Denmark and Sweden showed low rates of consumption (Box 1). To estimate the effect of differential age, a sensitivity analysis was carried out by studying the consumption in just the population aged 5 19 years in the 10 countries studied 20 and using these figures as the denominators in the calculation of DDD. The results obtained were very similar to using the total population 20 (eg, the US had an RR of 3.61 [95% CI, ] using the total population, whereas using the 5 19-year-old population gave an RR of 3.55 [95% CI, ]). This implies that the differences in RRs between countries cannot be explained by differences in the age distribution alone. 20 Comparison of trends from 1994 to 1997 and 1998 to 2000 in the total consumption of total licit dexamphetamine and methylphenidate in all countries, excluding Canada and the US, showed an overall 87% increase in consumption for the period compared with (RR, 1.87; 95% CI, ). For the US alone, the increase was 45% (RR, 1.45; 95% CI, ) and for Canada alone the increase was 93% (RR, 1.93; 95% CI, ). 540 MJA Vol November 2002

3 From 1994 to 2000, the patterns of psychostimulant consumption differed markedly between Australia and other countries. In 1994, for example, the methylphenidate to total psychostimulant consumption was 86% for the US, 94% for Canada and 38% for Australia. In 2000, this declined to 59% in the US and 84% in Canada, and was 42% in Australia. Australian jurisdictional analysis From 1984 to 2000, in Australia, there was a 26% increase per year in the total rate of consumption of dexamphetamine and methylphenidate per year (RR, 1.26; 95% CI, ). From 1994 to 2000, the rate of total psychostimulant consumption increased fold compared with the period Australia s total consumption of dexamphetamine over the period for all States (including Western Australia) showed an average increase of 31% per year (RR, 1.31; 95% CI, ) and a 30% per year increase for methylphenidate (RR, 1.30; 95% CI, ). The trend for WA s consumption of dexamphetamine increased by an average 43% per year over the period (RR, 1.43; 95% CI, ), while the total consumption for all jurisdictions (excluding WA) showed an average increase of 27% per year (RR, 1.27; 95% CI, ). Over the same period, average consumption of methylphenidate in WA increased by 20% per year (RR, 1.20; 95% CI, ), compared with a 19% per year increase for all other jurisdictions (RR, 1.19; 95% CI, ). The jurisdictional trends for the period are shown in Box 2. A comparison of trends in the consumption of dexamphetamine for the whole of Australia shows an overall 14- fold increase for the period compared with (RR, 13.93; 95% CI, ). For methylphenidate, there was a sixfold increase in consumption for the period compared with (RR, 6.30; 95% CI, ). The differences between jurisdictions are shown in Box 3. From 1994 to 2000, the patterns of consumption of psychostimulants differed considerably between jurisdictions. In 1994, methylphenidate comprised 47% of total psychostimulants consumed in NSW and 35% in WA, whereas in 2000 methylphenidate comprised 44% in NSW but had fallen to 15% in WA. From 1994 to 2000, the total licit psychostimulant consumption in the US, Canada and WA did not differ significantly (Box 4), but the annual average increase of 11% per year was highly significant (RR, 1.11; 95% CI, ). The rate of consumption of total licit psychostimulants in the US was higher, but not significantly more than in WA (RR, 1.43; 95% CI, ). Canada consumed less than WA, but again this was not significant (RR, 0.79; 95% CI, ). For the period , there was a 47% increase in consumption for the US, Canada and WA (RR, 1.47; 95% CI, ) compared with the period DISCUSSION 1.Discussion Our trend analyses form reference data for international and Australian jurisdictional comparisons of the consumption of licit psychostimulants. The advantage of standardising consumption in DDDs/1000 population per day is evident in the ability to compare the consumption of the individual or total psychostimulants between and within countries. Our results support the findings of large increases and high levels of consumption of psychostimulants in the US and Australia using a variety of other indicators of psychostimulant consumption, such as prescriptions or tablets dispensed, visits to doctors, and regional or national surveys of young people done in many settings, including schools. 1,6-14 The US s highest consumption of these agents, Canada s second, Australia s and New Zealand s equal third and the lower rankings have not been reported before. Factors contributing to high consumption in the US, in addi- 3: Rate ratios (RR) of total licit consumption of psychostimulants in New South Wales (1.0) compared with other Australian jurisdictions for Aust. Capital Territory (RR, 0.70; 95% CI, ) Northern Territory (RR, 0.76; 95% CI, ) Queensland (RR, 0.78; 95% CI, ) South Australia (RR, 0.94; 95% CI, Tasmania (RR, 0.94; 95% CI, Victoria (RR, 0.58; 95% CI, ) Western Australia (RR, 2.17; 95% CI, ) Australia (RR, 0.95; 95% CI, ) Source: Treaties and Monitoring Unit, Rate ratio : Standardised total licit consumption of psychostimulants in the United States, Canada and Western Australia, DDDs/1000 per day 8 United States 7 Canada Western Australia Year DDD = defined daily dose. Source: International Narcotics Control Board, 2001; Treaties and Monitoring Unit, MJA Vol November

4 tion to different age composition, may include the ready access to a wide range of community prescribers (eg, school nurses 8 and general community doctors), broader diagnostic criteria for ADHD, and prescribing standards less strict than, for example, those of the UK. 2,5 An international comparison showed that consumption in Europe is relatively low but rising. 9 Australia s national 1.8% point prevalence of psychostimulant consumption during 1998 in 6 17-year olds 10 and NSW s point prevalence in November 2000 of 1% in those aged under 18 years 14 are lower than rates in the US, but the reported differences in methodology, analyses and measures of use restrict comparisons. WA s highest rate of consumption in Australia, with levels similar to those in the US and Canada (Box 4), requires further analysis of contributing factors and defined outcomes. Researchers regard overtreatment of ADHD as unlikely in NSW, as the estimated 1% point prevalence of use in people younger than 18 years 14 is less than the 3% or higher rates of treatment often reported in US children. It is also much less than Australia s 11.2% annual prevalence of ADHD as defined by DSM-IV criteria, equivalent to a 7.5% point prevalence of ADHD in people aged 6 17 years. 7 Methodological differences between the studies, however, restrict comparisons. UK prescribing recommendations for psychostimulants (following or in conjunction with non-drug measures) 2,5 are confined to the severe combined-type of ADHD. This occurs with a point prevalence of about 1% of 6 16-year-olds, compared with Australia s 1.8% of 6 17-year-olds or the higher rates of ADHD treated in the US. 2,10 The high consumption of psychostimulants in WA raises the issue of their misuse. 6 Australia s Illicit Drug Reporting System reported a black market trade in illicit prescription amphetamines existed in all jurisdictions, with WA in 2001 having the highest rate (38%) in amphetamine-injecting drug users in the past six months. 21 In 2000, 17 (7.8%) of 217 students aged years in five WA government and nongovernment schools reported using non-medically prescribed psychostimulants in the past, mainly for non-medical reasons. 22 In Canada, where the level of psychostimulant consumption is similar to WA, 8.5% of students aged years reported in 1998 taking non-medically prescribed psychostimulants in the previous 12 months. 6 An estimated children, or 4.2% 4.5% of WA s population aged 4 17 years in 2000, received psychostimulants for ADHD in This equated to yearly estimates of million tablets of dexamphetamine and million methylphenidate tablets. 23 The Health Insurance Commission (HIC) and state pharmacy bodies have alerted community pharmacists to exercise diligence with the frequency of repeat prescriptions for dexamphetamine dispensed in a number of cases of ADHD. 24 The gradual decline in methylphenidate consumption in the US may reflect a growing realisation of the pharmacokinetics and price advantages of dexamphetamine. 1 In Australia, the high relative consumption of methylphenidate in NSW compared with WA implies differences in jurisdictional prescribing controls and, in NSW, the high prescribing and supply of methylphenidate through non-pbs channels such as hospitals, special clinics and private prescriptions. Our study was limited by the lack of data on age, sex, retention in treatment, indication and doses of the drugs. With these data, which are obtainable from the state departments of health and other sources, analytical studies may be applied to the health, economic and other outcome indicators arising from the different levels of psychostimulant consumption. The high rates of consumption of psychostimulants and evidence of their misuse in WA imply prescribers and pharmacists may be assisted by online information on drugs dispensed for ADHD patients before repeated prescribing and dispensing. Access may be facilitated, incorporating privacy provisions, by government agencies and pharmacies using compatible software. The differences in psychostimulant consumption within Australia are analogous to the heterogeneous patterns reported for the licit opioids. 16 Both groups are Schedule 8 drugs, the most strictly controlled agents in this country. An investigation appears warranted to locate the sources of referral, prescribing and supply, as well as the controls of prescribing in the jurisdictions, to identify the main causes of the differences in psychostimulant use and misuse in Australia These may be responsive to new national prescribing requirements or systems. ACKNOWLEDGEMENTS 1.Acknowledgements The Treaties and Monitoring Unit (Barton, ACT) provided annual data on the forms and strengths of dexamphetamine and methylphenidate in Australia by State and Territory from 1984 to The International Narcotics Control Board (Vienna, Austria) provided annual data in kg for dexamphetamine and methylphenidate consumed by each of the 10 countries from 1994 to COMPETING INTERESTS 1.Competing interests None identified. REFERENCES 1.References 1. Elia J, Ambrosini PJ, Rapoport JL. Drug therapy: treatment of attention-deficit-hyperactivity disorder. N Engl J Med 1999; 340: Stimulant drugs for hyperactivity in childhood. 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